Modified Project Summary/Abstract Section African American (AA) men are at a greater risk of developing aggressive prostate cancer (PrCa) than are Caucasian men. Therefore, identifying biomarkers involved in aggressive PrCa that can be used to identify AA men for specific and/or novel therapies would provide a major advance in public health. Consequently, there is intense effort to identify potential biomarkers that could independently predict poor clinical outcome and identify novel therapies for men with aggressive PrCa. Notably, heat shock proteins, PrCa Antigen 3, and Serine Protease Inhibitor Kazal-type 1, are all overexpressed in men with PrCa, where as Annexin II is suppressed. Despite the biological importance of these biomarkers, no studies have yet evaluated the significance of these biomarkers in AA men with aggressive PrCa. We believe that Howard's University Hospital urologic clinic which evaluates approximately 200 PrCa patients per year, is an ideal source for studying the importance of biomarkers as predictors of aggressive PrCa in AA men. We propose to evaluate the bi-directional expression of protein and gene signature pairs different in archival tissue samples from AA men who had been diagnosed with an aggressive form of PrCa at the Washington VA Medical Center and Howard and Johns Hopkins University Cancer Centers. The main hypothesis is that the bi-directional expression of genes and proteins is predictive of aggressive, lethal PrCa risk. To test this hypothesis we propose two aims. The first aim will test the hypothesis that microarray gene expression profiling produces bi-directional biomarker signature pairs that can be used to build a risk prediction model for PrCa. The second aim will test the hypothesis that the risk prediction of poor clinical outcome with bi-directional gene and protein expression pairs is superior to the use of a single gene or protein. Candidate pairs include those discovered in Aim 1. We anticipate that these studies may provide insight into selected genes and proteins as reliable predictive biomarkers for identifying aggressive PrCa in AA men, and could inform future human clinical applications for treatment of aggressive PrCa.